Biosimilarity to Reference Bevacizumab

ZIRABEV^® RECEIVED IT'S EMA LICENSE BASED ON THE TOTALITY OF EVIDENCE SUPPORTING HIGH SIMILARITY TO REFERENCE BEVACIZUMAB^2-5

The totality  of evidence supports comparability to reference bevacizumab^2-5

Abbreviations: CI=confidence interval. C_max=maximum concentration. AUC_0-t=area under the curve, from zero to the last quantifiable concentration. AUC_inf=area under the curve, from zero to infinity. NSCLC=non-small cell lung cancer. ORR=overall response rate. VEGF=vascular endothelial growth factor.

References:  

1. ZIRABEV® (bevacizumab) summary of product characteristics.
2. Reinmuth N, Bryl M, Bondarenko I, et al. BioDrugs. 2019;33(5):555-570. 
3. Knight B, Rassam D, Liao S, Ewesuedo R. Cancer Chemother Pharmacol. 2016;77(4):839-846. 
4. Data on file. Pfizer Inc., New York, NY. 2018. 
5. Rule K, Peraza M, Shiue M, et al. Poster 1217 presented at: IASLC 16th World Conference on Lung Cancer (WCLC 2015); September 6-9, 2015; Denver, CO. 

ZIRABEV^® IS HIGHLY SIMILAR IN STRUCTURE AND FUNCTION TO REFERENCE BEVACIZUMAB²

Structural similarity: identical primary amino acid sequence²

Peptide mapping data supported identical primary amino acid sequence for ZIRABEV^® and reference bevacizumab²

This was one of 5+ methods used to support primary structure analytical similarity.

Functional similarity: inhibition of VEGF-induced cell proliferation highly similar to that of reference bevacizumab²

Cell growth inhibition assay: dose-response curve at a constant VEGF concentration²

Abbreviations: VEGF=vascular endothelial growth factor.

Reference:

1. ZIRABEV® (bevacizumab) summary of product characteristics.
2. Rule K, Peraza M, Shiue M, et al. Poster 1217 presented at: IASLC 16th World Conference on Lung Cancer (WCLC 2015); September 6-9, 2015; Denver, CO. 

SIMILAR PK PROFILE TO REFERENCE BEVACIZUMAB IN HEALTHY SUBJECTS IN A 3-ARM STUDY² 

Median serum concentration-time profile following a single 5 mg/kg intravenous dose of ZIRABEV^®, EU-licensed Bevacizumab, or US-licensed Bevacizumab in healthy subjects² 

• The mean C_max , AUC_0-t , and AUC_inf  estimates and intersubject variability for each PK parameter were similar across the 3 study drugs²

  —  ZIRABEV vs Bevacizumab-EU: 90% CIs of PK parameters fell within the 80% to 125% bioequivalence window 
  —  ZIRABEV vs Bevacizumab-US: 90% CIs of PK parameters fell within the 80% to 125% bioequivalence window
  —  Avastin-US vs Bevacizumab-EU: 90% CIs of PK parameters fell within the 80% to 125% bioequivalence window 

Abbreviations: CI=confidence interval. C_max=maximum concentration. AUC_0-t=area under the curve, from zero to the last quantifiable concentration. AUC_inf=area under the curve, from zero to infinity. PK=pharmacokinetics.

Reference:

1. ZIRABEV® (bevacizumab) summary of product characteristics.
2. Knight B, Rassam D, Liao S, Ewesuedo R. Cancer Chemother Pharmacol. 2016;77(4):839-846. 
 

ZIRABEV^® IS LICENSED ACROSS ALL ELIGIBLE INDICATIONS OF REFERENCE BEVACIZUMAB THROUGH THE PROCESS OF EXTRAPOLATION²

Scientific justification supports extrapolation of all eligible indications of Avostin to ZIRABEV^®2

Abbreviations: CRC=colorectal cancer. PD=pharmacodynamics. PK=pharmacokinetics.

Reference: 

1. ZIRABEV® (bevacizumab) summary of product characteristics.
2. Data on file. Pfizer Inc., New York, NY. 2018.